At this stage of his career, Mawson became increasingly interested in ice age geology and an offer to join Sir Ernest Shackleton's 1907 Antarctic expedition was happily accepted. In that journey, named the Nimrod Expedition, Mawson was part of the first team to scale the volcanic Mount Erebus (the scene of a tragic Air New Zealand plane crash in 1979), as well as the first journey to the South Magnetic Pole. That expedition ignited a fascination with the continent that would see him return there several times up until 1931.

In 1911, when Roald Amundsen and Robert Falcon Scott were preparing for their heroic journeys to the South Pole, Mawson was approached by Scott to join his Terra Nova expedition. As Mawson was keen to chart the coastal area directly south of Australia, he put this proposal to Scott, but those plans could not be squeezed into Terra Nova's already full itinerary. Mawson turned down Scott's offer and made preparations for his own decidedly less glamorous expedition, which would turn out to include one of the greatest stories of polar survival.

Mawson's Australasian Antarctic Expedition arrived on the coast of Commonwealth Bay, directly south of Australia, in 1912. Three separate parties wintered over until the summer of 1912/13, at which stage their respective journeys could begin. Mawson was to travel with two others, Lieutenant Belgrave Ninnis and Dr Xavier Mertz. Their plan was to head east approximately 480 km (300 miles), high on a crevassed plateau, then return on a lower coastal route. They were to sled with husky teams and heavily laden sledges. The weather was horrific. On several occasions the team was stranded for days when they were buffeted by 115 kmh (70+ mph) winds, then on the 14th of December 1912, disaster struck. Ninnis, his team of huskies and his sledges plummeted into a crevasse. The only sign of life was a dog lying on a ledge some 150 feet down the newly opened chasm, past this was only silent darkness. Ninnis' sledges contained all the tents and most of the food. Mawson and Mertz had 10 days rations left and no shelter. They were 315 miles from safety.

The remaining pair immediately set off to return. A crude tent was fashioned by draping a tent cover over ski poles. Their rations were supplemented by eating the weaker of the huskies, especially the liver as they believed it was highly nutritious and consumed less fuel to cook. This was to be the second tragedy of the journey as unbeknownst to them, husky livers contain poisonous levels of vitamin A. As they ate more liver, they grew weaker and slowly slipped into madness.

By January 7, 1913, they were still 100 miles from base and Mertz, had grown incredibly weak and delirious. At one stage he actually removed his glove and attempted to bite off a finger. He died later that night. Mawson was now alone and losing his spirit, then he himself fell into a crevasse, but was saved when his sledge caught hold. He later stated that he considered cutting the rope. By the time he was nearing the base, the soles of his feet had sloughed away and had to be tied back on with strips of leather. Miraculously, he stumbled across a cairn with emergency rations and a note left by his fellow expiditioners. The note stated that he was now less than 50 miles from base and the expedition ship, the Aurora was waiting. When he finally arrived on February 8, 1913, he saw the Aurora steaming away as a speck on the horizon. A rear guard stayed in case any of the lost party returned and when Mawson reached the hut, he was in such bad physical shape, his men had to ask him to identify himself.

They group had to wait another 11 months for the Aurora's return. He was knighted on his arrival back to Australia in 1914 and wrote a book outlining the ill-fated expedition called The Home of the Blizzard (1915). He was appointed Professor of geology at the University of Adelaide in 1920. Mawson died on the 14th of October 1958 and was buried with a state funeral.

As part of Mawson's Antarctic endeavors, he enabled Australia to claim 6,475,000 square km (2,500,000 square miles) of Antarctica. His image appeared for a time on the Australian one hundred-dollar bill. He is remembered as one of the greatest of polar explorers.